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Am J Physiol Cell Physiol (March 20, 2002). doi:10.1152/ajpcell.00566.2001
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Articles in PresS, published online ahead of print March 20, 2002
Am J Physiol Cell Physiol, 10.1152/ajpcell.00566.2001
Submitted on November 26, 2001
Accepted on March 14, 2002

Protein kinase C regulates both the endocytosis and recycling of E-cadherin

Tam Luan Le1, Shannon R. Joseph2, Alpha S. Yap3, and Jennifer L. Stow1*

1 Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia; Department of Biochemistry, University of Queensland, Brisbane, Queensland, Australia
2 Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia
3 Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia; Department of Physiology and Pharmacology, University of Queensland, Brisbane, Queensland, Australia

* To whom correspondence should be addressed. E-mail: j.stow{at}imb.uq.edu.au.

E-cadherin is a major component of adherens junctions in epithelial cells. We have previously shown that a pool of cell surface E-cadherin is constitutively internalized and recycled back to the surface. In the present study, we investigated the potential role of protein kinase C (PKC) in regulating the trafficking of surface E-cadherin in MDCK cells. Using surface biotinylation and immunofluorescence, we found that treatment of cells with phorbol esters increased the rate of endocytosis of E-cadherin, resulting in accumulation of E-cadherin in apically-localized early or recycling endosomes. The recycling of E-cadherin back to the surface was also decreased in the presence of phorbol esters. Phorbol ester-induced endocytosis of E-cadherin was blocked by specific inhibitors, implicating novel PKC isozymes, such as PKC-{epsilon} in this pathway . PKC activation led to changes in the actin cytoskeleton facilitating E-cadherin endocytosis. Depolymerization of actin increased endocytosis of E-cadherin while the PKC-induced uptake of E-cadherin was blocked by the actin stabilizer jasplakinolide. Our findings show that PKC regulates vital steps of E-cadherin trafficking, its endocytosis and its recycling.




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